My main interest is the wiring of the nervous system: How is it established in the first place? Why does the nervous system become un-wired during neurodegenerative disease? My lab studies both of these problems, taking advantage of the simple nervous system of Drosophila.
Development: The core question in axon growth and guidance is to understand how cytoplasmic signaling networks modulate the cytoskeleton to cause an axon to grow in the right direction, in response to external cues. To find out, we do high-resolution live imaging of a single, identified neuron in the developing wing. By combining this with genetics, biochemistry and computational modeling, we can now trace the source of the final neuroanatomy of the wing all the way back to its basis in the physics of actin networks, and how these are modulated by biochemical signaling proteins to produce the cell biology of motility.
Neurodegeneration: To find a rational treatment for disease, we first have to disentangle the long list of cellular defects with which the degeneration process is associated. We have now shown that these defects fall into at least three, largely parallel pathways that interact synergistically to cause neuron loss. One is that the disease mechanism actually accelerates the absolute rate at which we age. In parallel, the immune system becomes hyperactivated and neurotoxic, while a third pathway destabilizes the axon cytoskeleton. It is the combination of all three effects that cause the loss of brain tissue during disease. Now that we know this, we can look for genes that will attenuate each pathway and restore neuron health.
